Molecular architecture of human tooth development: A network-based analysis of gene expression

Understanding the molecular mechanisms underlying tooth development is crucial for addressing developmental abnormalities. This study aimed to identify critical genes and pathways involved in human odontogenesis through comprehensive bioinformatic analysis. Gene expression data (GSE48150) comparing human embryonic tooth germs and lip samples were analyzed. Differentially expressed genes (DEGs) were identified using GEO2R (FDR < 0.01, |Log2FC| > 1). Protein-protein interaction networks were constructed using STRING and Cytoscape. Hub genes were identified through centrality metrics, and gene regulatory networks were analyzed using iRegulon. Functional enrichment analysis was performed using g: Profiler. Analysis identified 445 DEGs (138 upregulated, 307 downregulated) in tooth development. Network analysis revealed 21 hub genes, with TTN, PPARG, and MYOD1 showing the highest centrality metrics. The most affected molecular functions included structural constituents of muscle and cytoskeletal protein binding. Several Wnt pathway-interacting genes were identified as differentially expressed. This study revealed novel molecular mechanisms in tooth development, highlighting the unexpected involvement of muscle-related genes and pathways. The identified hub genes and transcription factors provide potential therapeutic targets for developmental dental and lip anomalies and offer new insights into the molecular basis of odontogenesis and development of lips.